Tuberculosis and non-pulmonary malignancies : study of ten cases.

INTRODUCTION: Tuberculosis (TBC) is a major public health problem with high mortality especially in developing countries. It is associated with a higher risk of developing pulmonary and non-pulmonary malignancies including solid and hematologic cancers. Association between TBC and nonpulmonary malignancies is rarely described in the literature. AIM: To describe the epidemiological, clinical, therapeutic modalities and the evolutive aspects of patients treated for cancer and TBC. METHODS: This is a retrospective study conducted over a period of 19 years (between 1993 and 2012), including 10 patients followed up for cancer and tuberculosis at the department of oncology and the department of infectious disease, CHU Habib Bourguiba Hospital and CHU HediChaker, Sfax, Tunisia. RESULTS: The average age of patients was 55 years old. The sex ratio was 1. The different locations of cancer were represented by the breast (4 cases), the nasopharynx (1 case), the colon (1 case), the kidney (1 case) the gum (1 case), the endometrium (1 case) and the blood (1 case).TBC and cancer were synchronous in 5 cases. Concerning the metachronous presentation that interested 5 patients, the average time betweenthe onset of TBC after cancer diagnosis was 3.5 years. Three of these patients were treated by chemotherapy with radiation therapy. TBClocalization was nodal in 6 cases, spinal one case, nasopharyngeal in one case, peritoneal in one case and urogenital in one case. The diagnosisof TBC was made incidentally in two cases during axillary lymph node dissection. The therapeutic management of cancer was based on surgery,chemotherapy and / or radiotherapy. All patients received anti TBC treatment for at least six months. Surgery was indicated in one case(laminectomy). A complete remission of cancer was observed in 9 patients. Concerning TBC, recovery was observed in 8 patients, 1 patient hada spinal recurrence and 1 patient is being treated. CONCLUSION: Chronic inflammation during TBC can lead to cancer development. The etiopathogenesis of this association is still imperfectly known. Association between TBC and non-pulmonary cancer, although rare, should be always kept in mind in order to handle in time these two diseases in order provide the best chances of recovery for patients.

Cardiac metastases: 4 cases report.

Cardiac metastases are rare. They are found in one to 10% of autopsies of patients withmalignant neoplasm. Adenocarcinoma represents the most common histologicaltype. The most common neoplasms that metastasize to the heart are lung andbreast cancers, melanoma, mesothelioma and lymphoma. However, Cardiacinvolvement is unusual in Hepatic, cutaneous and gastric cancer. We reportedthese three primary localizations in our cases.

Tunisian adult's Hodgkin lymphoma Study Group.

The Tunisian adult's Hodgkin lymphoma (HL) Study Group was created in 1999. It aimed to improve the management of this curable hematologic malignancy by standardizing the diagnosis, assessment of disease, treatment management and therapeutic evaluation in different Tunisian centers (Hematology, oncology and radiotherapy).Since 1998, four versions of the prospective national protocol for treating adult Hodgkin lymphoma have succeeded (MDH99, MDH2002, MDH2008, MDH2015). Each version was based on the results of the previous version and analyzed according to new data from the literature. Due to this national study group, the number of patients lost to follow decreased significantly (30% before the creation of the group and only 3% for patients treated with MDH2008), the complete and uncertain response rates have improved (75% before the creation of the group and 92% in patients treated with MDH2008) with dramatically improved rates of overall survival from 57% to 90%. On the other hand there was an improvement of toxic death rate (13% of toxic deaths in MDH2002 to 4.37% in the MDH2008) with a decrease of the respective rate of primary failure and relapse by 17% and 12.5% in MDH2002 against the 11.4% and 7.8% in the MDH2008. This resulted in an improvement in overall survival (90%) and event-free survival at 5 years (75%). Now with the introduction of positron emission tomography in Tunisia, we hope yet to finalize the assessment of response and thus better adapt the treatment of this disease. Our objective remains the improvement of event-free survival rate to reach 80%.

Chemotherapy-induced peripheral neurotoxicity: single-centre prospective study.

OBJECTIVE: Chemotherapy-induced peripheral neurotoxicity (CIPN) ranges from simple paresthesia to paralysis, which may be transient or irreversible. The aim of our study was to detect CINP in our patients undergoing chemotherapy and to study the cumulative neurotoxic doses for the different drugs. METHODS: This is a cross-sectional prospective study carried out in the medical oncology department of the Habib Bourguiba University Hospital in Sfax. A survey was conducted to detect and explore possible chemo-induced peripheral neuropathy in patients undergoing known potentially neurotoxic anti-cancer treatments. RESULTS: Seventy-three patients were included in the study. The average age was 51.8 years (13-80 years). The prevalence of CIPN was 52.1%. CIPN was classified as grade I in 24 (63.2%) cases and grade II in 14 (36.8%) cases. No grade III or IV peripheral neuropathy was detected in our patients. Paclitaxel was the drug with the highest incidence of CIPN (76.9%). The chemotherapy (CT) protocols most prone to chemotherapy-induced peripheral neurotoxicity (CIPN) were based on taxanes (47.3%) and oxaliplatin (59%). Paclitaxel was the drug most likely to cause CIPN (76.9%) (p=0.031). Paclitaxel single dose per cycle of 175 mg/m2 (66.67%) was more associated with the occurrence of CIPN than 80 mg/m2 (40%), but without significant difference (p=0.437). The average cumulative dose was estimated at 315 mg/m2 for docetaxel, 474 mg/m2 for oxaliplatin and 579 mg/m2 for paclitaxel (p=0.16). CONCLUSION: The prevalence of NPCI was 51.1% in our series. Oxaliplatin and taxanes were the main contributors to this complication with cumulative dose over than 300 mg/m2.

Prognostic factors of male breast cancer: A monocentric experience.

BACKGROUND: Male breast cancer (MBC) is a rare malignancy presenting only 1% of all breast cancer. The purpose of this study was to analyze clinical and pathological prognostic factors of MBC. METHODS: This is a retrospective study including 32 men diagnosed and treated for a primary breast cancer at the department of medical oncology in Sfax between 2005 and 2020. RESULTS: The incidence of MBC was 1.3%. The median age of our patients was 55 years (range: 29-85 years). The average tumor size of 3.9 cm. Lymph nodes involvement was present in 18 cases (56.2%) with capsular rupture in 52% cases. Tumor was grade II in 71.8 % of cases. The expression of hormonal receptors was founded in 100% of cases. Two patients had an overexpression of HER2 (6.2%). There was no case of triple negative MBC. The OS at 5 and 10 years was 67.8% and 30.8% respectively. Prognostic factors were T4 (p = 0.015), involved nodes (p = 0.035), M+ (p = 0.01), SBR III (p = 0.0001) and HER2+++ (p = 0.001). CONCLUSION: Contrary to breast cancer in women, our study showed that Tunisian MBC have positive hormone receptors in all cases. Although the overexpression of HER2 was low (8.33%) and there was no case of triple negative MBC, the prognosis was poor because of T4 stage, involved nodes, SBR III and distant metastases.

Prognostic factors in metastatic nasopharyngeal carcinoma.

INTRODUCTION: Nasopharyngeal carcinoma has the highest metastatic potential of all head and neck cancers. The survival time of patients with nasopharyngeal carcinoma has improved significantly in the last decades due to the use of combination of chemotherapy and radiotherapy, as well as advances in radiotherapy techniques. However, appropriately 30% of patients with nasopharyngeal carcinoma suffer a poor prognosis, mainly due to distant metastasis. OBJECTIVE: The study aimed to identify the survival and prognostic factors in metastatic nasopharyngeal carcinoma. METHODS: A retrospective analysis was conducted in patients treated for synchronous metastatic nasopharyngeal carcinoma or metachronous metastatic nasopharyngeal carcinoma for 14 years (2003-2016). Overall survival was analyzed using the Kaplan-Meier method and compared using the log-rank test for the whole population and both groups of patients. Multivariate analysis was performed using the Cox model; p-values < 0.05 were considered to indicate statistical significance. RESULTS: One hundred and twelve patients with metastatic nasopharyngeal carcinoma were included (51 patients with metastatic nasopharyngeal carcinoma, and 61 patients with metachronous metastatic nasopharyngeal carcinoma). In the whole population, the median overall survival was 10 months (1-156 months). In the multivariate analysis, female gender, poor performance status (WHO > 1) and metachronous metastasis were independent prognostic factors. In the metastatic nasopharyngeal carcinoma patients, the median overall survival was 13 months (1-156 months). In multivariate analysis, independent prognostic factors were non-oligometastatic disease, severe (G3‒G4) chemotherapy toxicity and the lack of nasopharyngeal and metastatic site irradiation. In the metachronous metastatic nasopharyngeal carcinoma patients, the median overall survival was 7 months (1-41 months). In multivariate analysis, the poor performance status (WHO > 1) was an independent metastatic nasopharyngeal carcinoma prognostic factor. CONCLUSION: Oligometastatic patients with synchronous metastatic nasopharyngeal carcinoma had better survival. The locoregional treatment of primitive nasopharyngeal carcinoma improved survival in patients with metastatic nasopharyngeal carcinoma who responded to induction chemotherapy. Local irradiation of metastatic sites improved survival of metastatic nasopharyngeal carcinoma patients. Grade 3 or 4 chemotherapy toxicity altered survival among patients with synchronous metastatic nasopharyngeal carcinoma.

Prognostic factors in inflammatory breast cancer: A single-center study.

BACKGROUND: Previous studies have shown that poor prognostic indicators of inflammatory breast cancer (IBC) include younger age at diagnosis, poorer tumor grade, negative estrogen receptor, lesser degree of pathological response in the breast and lymph nodes. METHODS: This is a retrospective study conducted over a period of 12 years between January 2008 and December 2019 at the medical oncology department at Habib Bourguiba University Hospital in Sfax. We included in this study women with confirmed IBC. We excluded patients with no histological evidence, those whose medical records were unusable. Data collection was done from patient files. The aim of this study was to analyze the factors of poor prognosis of this entity. RESULTS: During a period of 12 years (2008-2019), 2879 cases of breast cancer were treated at Habib Bourguiba hospital in Sfax. 81 IBC were included. The incidence of IBC was 3%. The average age was 52.4 years (26-87 years). Invasive ductal carcinoma was the most frequent histological type (85.7%). Hormone receptor were positive in 64%. Human Epidermal Growth Factor Receptor-2 (HER2) was overexpressed in 35.9% of cases. The proliferation index Ki-67 was analyzed in 34 cases. It was >20% in 24 cases. Luminal A, luminal B, HER2+++, triple negative were found in 13%, 50.7%, 16% and 20% respectively. Metastases at diagnosis were found in 38%. Poor prognostic factors significantly influencing overall survival in univariate analysis were metastatic stage, high SBR grade, lymph node involvement, in particular greater than 3 nodes, negative hormone receptors, triple-negative molecular profile and occurrence of relapse. CONCLUSION: Number of positive lymph nodes greater than 3 and the occurrence of relapse were independent prognostic factors in case of localized IBC. Metastatic stage was associated with a very poor prognosis.

Self-medication with herbal medicine and breast cancer survival: a prospective monocentric study.

PURPOSE: The use of complementary and alternative medicine (CAM) is common among breast cancer patients, but less is known about whether CAM influences breast cancer survival. The primary aim of this study was to determine the impact of self-use of herbs on the overall survival. METHODS: This was a prospective study including 110 patients with breast cancer. All patients were questioned about the concept of taking herbs. We analyzed the demographic data and the overall survival. RESULTS: The average age was 51 years (30-80 years old). 37 had metastatic disease (33.6%). 48 patients had taken plants (43.6%). 19 patients consumed Graviola (39.6%) and 29 Alenda (60.4%). Overall survival at 3 years and at 5 years were, respectively, 96.2% and 82.4% in the absence of plant consumption versus 78.5% and 78.5% in case of plant consumption (p = 0.015). CONCLUSION: This study concluded that self-medication with Graviola or Alenda may be associated with an increase of death risk in patients with breast cancer. Further studies are needed to confirm these results.

Local and Lymph Node Relapse of Nasopharyngeal Carcinoma: A Single-Center Experience.

OBJECTIVES: The study aimed to investigate the epidemiological and clinical characteristics as well as the therapeutic results in patients with locoregional (LR) relapse after treatment of nasopharyngeal carcinoma (NPC). METHODS: We retrospectively reviewed the medical records of patients with local and/or regional recurrent NPC over 13 years (2003-2015). RESULTS: Twenty-five patients were treated for local or/and local-regional recurrence of NPC. The rate of LR relapse was 7.2%. The mean age of the patients was 46 ± 13.9 years. The median time to relapse was 25 months. The recurrence was nasopharyngeal in 17 patients, nasopharyngeal and neck lymph nodes in 7 patients, and neck lymph nodes in 1 patient. Fifteen relapsed patients had a locally advanced disease (rT3-rT4). Patients who had initially T1 or T2 tumor had a locally advanced relapsed disease (rT3rT4) in 27.3% and patients whose disease was initially classified as T3 or T4 had a locally advanced relapsed disease (rT3T4) in 85.7% (P = .005, Fisher test). Twelve patients had chemotherapy after relapse. Chemotherapy was followed by concurrent chemoradiotherapy in 3 patients and by radiotherapy (RT) in 4 patients. Nine patients had concurrent chemoradiotherapy and 1 patient had exclusive RT. The overall survival (OS) at 1 year, 3 years, and 5 years was, respectively, 58%, 18%, and 10%. The OS was significantly higher in patients with good performance status at the time of relapse (World Health Organization = 1; P = .01) and in patients with late relapse (after 2 years; P = .03). CONCLUSIONS: Locoregional relapse rate in our study was 7.2%. Locoregional reirradiation was the mainstay treatment modality in relapsed NPC. Relapsed NPC had a poor prognosis with a 5-year survival rate of 18%. The OS was significantly higher in patients with good performance status and in patients with late relapse (after 2 years).

Aggressive nasal-type natural killer/T-cell lymphoma associated with Epstein Barr virus presenting as testicular tumor.

BACKGROUND: Testicular lymphoma is a lethal disease with a median survival of approximately 12 to 24 months. Nasal-type natural killer/T-cell lymphoma of the testis is exceptional whether as a primary or secondary tumor. AIM: The authors report on the comprehensive histopathologic, immunohistochemical and molecular analysis of a case of primary testicular nasal type NK/T cell lymphoma and review the features of previously reported cases. OBSERVATION: We report a case of primary nasal-type natural killer/T-cell lymphoma of testis in a 28-year-old male. The histopathological examination of the surgical specimen, showed a large lymphoma cells with angioinvasion expressing CD3 (cytoplasmic), CD2, CD8, CD43, CD45, CD45Ro, CD56, T-cell intracellular antigen-1, perforine, Mib1 and granzyme. In situ hybridation for Epstein-Barr-virus- encoded mRNA was positive. Polymerase chain reaction study of formalin-fixed tissue showed lack of T-cell receptor gene rearrangements. The initial stage was I (EA) of Ann Arbor. This lymphoma was refractory to chemotherapy. The patient developed lymph node metastases in the out iliac and in the subclavicular region two months later. He died of disease after eight months. CONCLUSION: This study confirms that testicular NK/T-cell lymphoma deserves to be distinguished from the other testicular lymphomas. In fact, this lymphoma tends to occur at young age, to disseminate early, to have an aggressive course, and is strongly associated with EBV.

A Prospective Study About Trastuzumab-induced Cardiotoxicity in HER2-positive Breast Cancer.

BACKGROUND: Trastuzumab improves therapeutic outcomes among patients with human epidermal growth factor receptor 2-positive breast cancer (BC). However, it is associated with a risk of treatment-induced cardiotoxicity. The aims of this study were to determine the frequency of trastuzumab-induced cardiotoxicity (TIC) in Tunisian patients, to study the effects of trastuzumab on cardiac biomarkers and echocardiographic parameters using the speckle tracking technique and to identify risk factors of occurrence of TIC. PATIENTS AND METHODS: Fifty women with newly diagnosed human epidermal growth factor receptor 2-positive BC treated with or without anthracycline followed by taxane and trastuzumab were enrolled, from November 2016 to December 2018, to be evaluated every 3 months during trastuzumab treatment (total of 15 mo) using echocardiograms and blood samples. Left ventricular ejection fraction (LVEF) and peak systolic left ventricular longitudinal myocardial strain were calculated. Ultrasensitive troponin I (TNI) and N-terminal pro-B-type natriuretic peptide (NT pro-BNP) were also measured. RESULTS: LVEF decreased from 62±3.12% to 59±3.3% (P=0.005) over 15 months. Seven patients (14%) developed cardiotoxicity, as defined by the European Society of Cardiology; of these patients, 2 (4%) had symptoms of heart failure. Hypertension, left ventricular longitudinal myocardial strain, Log TNI, and NT pro-BNP measured at the completion of anthracyclines were significantly correlated to TIC occurrence. At multivariate analysis, the degree of LVEF decline was the only independent factor correlated to TIC (hazard ratio=2.4; 95% confidence interval=1.2-6.03; P=0.049). This TIC was reversible in 86% of cases. CONCLUSION: In patients with BC treated with trastuzumab, in addition to the evaluation of the LVEF, systolic longitudinal strain, TNI, and NT pro-BNP measured at the completion of anthracyclines are useful in the prediction of subsequent TIC.

Ovarian Cancer and Breast Metastases: A Diagnostic Dilemma.

Metastases of ovarian carcinoma to the breast are uncommon. The incidence of ovarian metastasis to the breast ranges from 0.5% to 1.2%. Nevertheless, its detection and distinction from other primaries, especially primary breast carcinoma, is important as treatment and prognosis differ significantly. We report the case of a 38-year-old Tunisian woman with bilateral metastases to breast from ovarian carcinoma. Through a review of literature, we discuss the clinical, radiological and histological characteristics of ovarian metastases to the breast.

[Neoadjuvant chemotherapy with concurrent chemoradiotherapy in the treatment of nasopharyngeal cancer: Southern Tunisian experience]. / La chimiothérapie néoadjuvante associée à la chimioradiothérapie concomitante dans le traitement du cancer du nasopharynx : expérience du Sud-Tunisien.

PURPOSE: A retrospective study to evaluate the efficacy and safety of the addition of neoadjuvant chemotherapy to concurrent chemoradiotherapy in the treatment of nasopharyngeal carcinoma. PATIENTS AND METHODS: Data from 62 patients treated for non-metastatic nasopharyngeal carcinoma were analyzed by comparing two groups of patients: a first group of 32 patients treated with 3 cycles of neoadjuvant chemotherapy based on docetaxel, cisplatin and 5-fluoro-uracil every 21 days followed by concurrent chemoradiotherapy (weekly cisplatin 40mg/m2 with radiotherapy 70Gy, 2Gy per session, 5 sessions per week) and a second group of 30 patients treated with the same concurrent chemoradiotherapy. RESULTS: After a median follow-up of 53.5 months, neoadjuvant chemotherapy showed a significant reduction in the rate of a distant metastatic relapses (3.3% vs. 10%, P=0.03). No significant difference in disease-free survival at 5 years (65.6% vs. 68.8%, P=0.46) or overall survival at 5 years (68.8% vs. 73.3%, P=0.46) was noted between the two groups. Induction chemotherapy was associated with febrile neutropenia of 15.6%. During concurrent chemoradiotherapy, hematological complications were greater in the first chemotherapy group (53% vs. 33%). CONCLUSION: Induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil is a safe and effective option in the treatment of nasopharyngeal carcinoma. A better definition of high risk of relapse group would optimize the indications of this chemotherapy in the therapeutic arsenal.

[Tunisian National Protocol for Adult Hodgkin's Lymphoma Treatment: Results of a therapeutic regimen adapted to the 2-cycle CT response, about 444 patients]. / Protocole national Tunisien prospectif de traitement du Lymphome de Hodgkin de l'adulte : résultats d'un schéma thérapeutique adapté à la réponse par tomodensitométrie à 2 cycles, à propos de 444 patients.

OBJECTIVE: In Tunisia, the management of Adult Hodgkin's Lymphoma (HL) has been standardized since 1999. We propose in this study to report the therapeutic results of the national protocol of adult HL treatment (MDH2008). PATIENTS AND METHODS: Our study is prospective multicenter interesting 444 patients followed for HL between July 2008 and June 2013 and treated according to the MDH2008 protocol. The median age of our patients was 30 years. B symptoms were present in 62.8 % of our patients. According to the Ann Arbor classification, our patients were in stages I, II, III and IV in 3 %, 42 %, 26 % and 29 %, respectively. The MDH2008 protocol is based on a strategy adapted to the therapeutic response to 2 cycles of chemotherapy. RESULTS: Response≥75 % to 2 courses of chemotherapy was achieved in 43 % of patients and the response rate at the end of treatment was 92.1 %. Forty-eight patients (11.4 %) had primary failure. In the multi-variant study, bulky mediastinal mass (IMT≥0.35) was an independent predictive factor of primary failure (P: 0.000). Nineteen toxic deaths (4.35 %) were reported. The relapse rate was 7.8 %. Event free survival, relapse-free survival and overall survival at 5years were 75 %, 89 % and 90 %, respectively. Adaptation of the treatment to the 2 cycles response was effective in unfavorable early stages and advanced stages. CONCLUSION: Compared to MDH2002 (second version of Tunisian prospective protocol), the MDH2008 reduced the primary failure rate, the rate of toxic deaths with escalated BEACOPP and the rate of relapse in Tunisian patients.

Epstein-Barr virus-targeted immunotherapy for nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) is constantly present in undifferentiated and poorly-differentiated nasopharyngeal cancer. Thus, tumour-associated viral antigens are potential targets for immunotherapy. Recently, both preclinical and early clinical studies have shown that various strategies can enhance EBV-specific immunity. Moreover, significant anti-tumour effect has been observed, and was generally correlated with biological response. The present review discusses the rational for EBV-targeted immunotherapy and summarises the latest developments in this area.

Results of a prospective randomised trial comparing conventional radiotherapy to split course bifractionated radiation therapy in patients with nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: Nasopharyngeal carcinoma (NPC) is generally responsive to radiation therapy. However therapeutic results after conventional radiotherapy remain relatively poor especially for patients with locoregional advanced NPC. The aim of this study was to evaluate the impact of a split course bifractionated radiotherapy regimen in a phase III randomised trial. PATIENTS AND METHODS: From January 1997 to September 2003, 154 patients with M0 histologically proven NPC were treated in our institution. They were staged according to the American Joint Committee on Cancer - International Union Against Cancer (AJCC-UICC) 1986 TNM classification. Patients with locally advanced nodal disease (N2-N3) received induction chemotherapy. All patients were randomised to receive either conventional radiotherapy at 2 Gy/fraction/day, 5 days/week to 70 Gy/7 weeks or split course bifractionated radiotherapy at 1.6 Gy/fraction, twice daily, 5 days/week to 70.4 Gy/6 weeks. Response and toxicity were evaluated according to the WHO and RTOG criteria. RESULTS: Patients were well balanced between the two arms. The complete remission rate was 91% in conventional radiotherapy arm and 93% in bifractionated radiotherapy arm (p=0.3). There was more grade II-III skin fibrosis in experimental arm with a 5 year actuarial probability of 66% vs 52% (p=0.04). Locoregional and distant relapses occurred in 34% of cases in conventional arm and 38% in experimental arm (p=0.28). With a median follow-up of 56 months, the 5 year overall survival and the disease free survival rates were, respectively (71% and 61%), in conventional arm and (62% and 60%) in bifractionated arm, the difference being statistically non significant. COMMENTS: The present trial comparing conventional radiotherapy to a split course bifractionated radiation therapy failed to demonstrate significant improvement in locoregional control and survival in experimental arm which was associated with more grade II-III skin fibrosis.

Proline homozygosity in codon 72 of TP53 is a factor of susceptibility to nasopharyngeal carcinoma in Tunisia.

A common polymorphism at codon 72 of TP53, the gene encoding the tumor suppressor protein p53, encodes either arginine or proline. These variants may be associated with tumor susceptibility since they interfere with the ability of TP53 to activate apoptosis, and might account for ethnic variation in cancer frequency. Using a polymerase chain reaction-restriction fragment length polymorphism assay, we tested peripheral blood samples from 115 patients with nasopharyngeal carcinoma (NPC) and from 83 healthy individuals. Patients with NPC (Arg/Arg = 38.26%, Arg/Pro = 41.73%, and Pro/Pro = 20%) showed a significantly different percentage of the Pro/Pro genotype, compared with the control population (Arg/Arg = 39%, Arg/Pro = 54%, and Pro/Pro = 7%) (P = 0.0307). No significant difference was observed between TP53 codon 72 polymorphism and age, sex, histological grade, and metastasis. These results provide evidence that individuals with the Pro/Pro genotype have an increased risk of developing NPC in Tunisia.

Prognostic factors in metastatic nasopharyngeal carcinoma / Fatores prognósticos no carcinoma nasofaríngeo metastático

Abstract Introduction: Nasopharyngeal carcinoma has the highest metastatic potential of all head and neck cancers. The survival time of patients with nasopharyngeal carcinoma has improved significantly in the last decades due to the use of combination of chemotherapy and radiotherapy, as well as advances in radiotherapy techniques. However, appropriately 30% of patients with nasopharyngeal carcinoma suffer a poor prognosis, mainly due to distant metastasis. Objective: The study aimed to identify the survival and prognostic factors in metastatic nasopharyngeal carcinoma. Methods: A retrospective analysis was conducted in patients treated for synchronous metastatic nasopharyngeal carcinoma or metachronous metastatic nasopharyngeal carcinoma for 14years (2003-2016). Overall survival was analyzed using the Kaplan-Meier method and compared using the log-rank test for the whole population and both groups of patients. Multivariate analysis was performed using the Cox model; p-values < 0.05 were considered to indicate statistical significance. Results: One hundred and twelve patients with metastatic nasopharyngeal carcinoma were included (51 patients with metastatic nasopharyngeal carcinoma, and 61 patients with metachronous metastatic nasopharyngeal carcinoma). In the whole population, the median overall survival was 10 months (1-156 months). In the multivariate analysis, female gender, poor performance status (WHO > 1) and metachronous metastasis were independent prognostic factors. In the metastatic nasopharyngeal carcinoma patients, the median overall survival was 13 months (1-156 months). In multivariate analysis, independent prognostic factors were non-oligometastatic disease, severe (G3-G4) chemotherapy toxicity and the lack of nasopharyngeal and metastatic site irradiation. In the metachronous metastatic nasopharyngeal carcinoma patients, the median overall survival was 7 months (1-41 months). In multivariate analysis, the poor performance status (WHO > 1) was an independent metastatic nasopharyngeal carcinoma prognostic factor. Conclusion: Oligometastatic patients with synchronous metastatic nasopharyngeal carcinoma had better survival. The locoregional treatment of primitive nasopharyngeal carcinoma improved survival in patients with metastatic nasopharyngeal carcinoma who responded to induction chemotherapy. Local irradiation of metastatic sites improved survival of metastatic nasopharyngeal carcinoma patients. Grade 3 or 4 chemotherapy toxicity altered survival among patients with synchronous metastatic nasopharyngeal carcinoma.

Resumo Introdução: O carcinoma nasofaríngeo tem o maior potencial metastático de todos os tipos de câncer de cabeça e pescoço. O tempo de sobrevida dos pacientes com carcinoma nasofaríngeo melhorou significativamente nas últimas décadas devido ao uso combinado de quimioterapia e radioterapia e os avanços nas técnicas de radioterapia. No entanto, aproximadamente 30% dos pacientes com carcinoma nasofaríngeo têm um prognóstico ruim, principalmente devido a metástases a distância. Objetivo: Identificar a sobrevida e os fatores prognósticos no carcinoma nasofaríngeo metastático. Método: Foi feita uma análise retrospectiva de pacientes tratados por carcinoma nasofaríngeo metastático sincrônico ou carcinoma nasofaríngeo metastático metacrônico por 14 anos (2003-2016). A sobrevida global foi analisada pelo método de Kaplan-Meier e comparada pelo teste de log-rank para toda a população e ambos os grupos de pacientes. A análise multivariada foi feita com o modelo de Cox; valores de p < 0,05 foram considerados como significância estatística. Resultados: Foram incluídos 112 pacientes com carcinoma nasofaríngeo metastático (51 com carcinoma nasofaríngeo metastático sincrônico e 61 com carcinoma nasofaríngeo metastático metacrônico). Em toda a população, a mediana da sobrevida global foi de 10 meses (1-156 meses). Na análise multivariada, sexo feminino, baixo status de desempenho (OMS > 1) e metástase metacrônica foram fatores prognósticos independentes. Nos pacientes com carcinoma nasofaríngeo metastático sincrônico, a mediana da sobrevida global foi de 13 meses (1-156 meses). Na análise multivariada, os fatores prognósticos independentes foram doença não oli-gometastática, toxicidade grave à quimioterapia (G3 - G4) e falta de irradiação nasofaríngea e do sítio metastático. Nos pacientes com carcinoma nasofaríngeo metastático metacrônico, a mediana da sobrevida global foi de 7 meses (1-41 meses). Na análise multivariada, o baixo status de desempenho (OMS > 1) foi um fator prognóstico independente. Conclusão: Pacientes oligometastáticos com carcinoma nasofaríngeo metastático sincrônico tiveram melhor sobrevida. O tratamento locorregional do carcinoma nasofaríngeo primário melhorou a sobrevida em pacientes com carcinoma nasofaríngeo metastático sincrônico que responderam à quimioterapia de indução. A irradiação local dos locais metastáticos melhorou a sobrevida dos pacientes com carcinoma nasofaríngeo metastático. A toxicidade de quimioterapia de grau 3 ou 4 alterou a sobrevida entre pacientes com carcinoma nasofaríngeo metastático sincrônico.